Intra-articular bupivacaine and morphine for knee osteoarthritis analgesia. Comparative study

Abstracts

JUSTIFICATIVA E OBJETIVOS: A osteoartrite é a mais freqüente entre as doenças articulares em pessoas idosas. O objetivo do estudo foi comparar o efeito analgésico da bupivacaína e da morfina por via intra-articular em pacientes portadores de osteoartrite de joelho. MÉTODO: Foram avaliados 39 pacientes em estudo duplamente encoberto, divididos de forma aleatória, em dois grupos: os do G1 (n = 18) receberam 1 mg (1 mL) de morfina diluída em 9 mL de solução fisiológica a 0,9% e os do G2 (n = 21), 25 mg (10 mL) de bupivacaína a 0,25% sem vasoconstritor, por via intra-articular. A intensidade da dor foi avaliada pela escala numérica e verbal nos momentos 0, 30, 60 minutos e 7 dias, em repouso e em movimento. Foram avaliados a necessidade de complementação analgésica com paracetamol (500 mg), a dose total de analgésico utilizado, a duração da analgesia e a qualidade da analgesia (pelo paciente). RESULTADOS: Dos 39 pacientes, 31 completaram o estudo. Não houve diferença significativa da intensidade da dor em repouso e em movimento entre os dois grupos nos momentos estudados. Não houve diferença entre os dois grupos no tempo entre a administração da solução e a necessidade de complementação analgésica. A dose média do paracetamol utilizada no primeiro dia da semana foi de 796 mg do G1 e de 950 mg no G2; a complementação na semana foi de 3578 mg no G1 e 5333 mg no G2. CONCLUSÕES: O efeito analgésico de 1 mg de morfina e de 25 mg de bupivacaína a 0,25% sem vasoconstritor intra-articular foram semelhantes.

ANALGESIA; ANALGÉSICOS; ANALGÉSICOS; ANESTÉSICOS; ANESTÉSICOS; DOR; DOR

SCIENTIFIC ARTICLE

Intra-articular bupivacaine and morphine for knee osteoarthritis analgesia. Comparative study ^*

Estudio comparativo de la analgesia entre bupivacaína y morfina intra-articular en osteoartritis de la rodilla

Miriam C B Gazi, M.D.^I; Adriana Machado Issy, M.D.^II; Rioko Kimiko Sakata, TSA, M.D.^II

^IEspecialista em Dor e Anestesiologista da UNIFESP

^IIProfessor Adjunto da Disciplina de Anestesiologia, Dor e Terapia Intensiva da UNIFESP

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: Osteoarthritis is the most common joint disease among elderly people. This study aimed at comparing the analgesic effects of intra-articular bupivacaine and morphine in knee osteoarthritis patients.

METHODS: Thirty-nine patients were included in this randomized double-blind study and divided in two groups: G1 (n = 18) patients were given intra-articular 1 mg (1 mL) morphine diluted in 9 mL of 0.9% saline, while G2 (n = 21) received intra-articular 25 mg (10 mL) of 0.25% plain bupivacaine. Pain intensity was evaluated by numerical and verbal scale at 0, 30, 60 minutes and 7 days at rest and in movement. Evaluated parameters were analgesic supplementation requirement with paracetamol (500 mg), total analgesic dose throughout the study, analgesia duration and quality (according to patient).

RESULTS: From 39 patients, 31 have completed the study. There has been no significant difference in pain intensity at rest and in movement between groups in all studied moments. There has been no difference between groups in time between solution administration and need for analgesic supplementation. Mean paracetamol dose in the first day was 796 mg for G1 and 950 mg for G2; supplementation during the week was 3578 mg for G1 and 5333 mg for G2.

CONCLUSIONS: The analgesic effect of intra-articular 1 mg morphine and 25 mg of 0.25% plain bupivacaine was similar.

Key Words: ANALGESIA: intra-articular; ANALGESICS, Opioid: morphine; ANESTHETICS: Local: bupivacaine; PAIN, Cronic: osteoarthritis

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La osteoartritis es la más frecuente entre las enfermedades articulares en personas de edad. El objetivo del estudio fue comparar el efecto analgésico de la bupivacaína y de la morfina por vía intra-articular en pacientes portadores de osteoartritis de rodilla.

MÉTODO: Fueron evaluados 39 pacientes en estudio doblemente encubierto, divididos de forma aleatoria, en dos grupos: los del G1 (n = 18) recibieron 1 mg (1 mL) de morfina diluida en 9 mL de solución fisiológica a 0,9% y los del G2 (n = 21) 25 mg (10 mL) de bupivacaína a 0,25% sin vasoconstrictor, por vía intra-articular. La intensidad del dolor fue evaluada por la escala numérica y verbal en los tiempos 0, 30, 60 minutos y 7 días, en reposo y en movimiento. Fueron evaluados la necesidad de complementación analgésica con paracetamol (500 mg), la dosis total de analgésico utilizado, la duración de la analgesia y la calidad de la analgesia (por el paciente).

RESULTADOS: De los 39 pacientes estudiados, 31 completaron el estudio. No hubo diferencia significativa de la intensidad del dolor en reposo y en movimiento entre los dos grupos en los tiempos estudiados. No hubo diferencia entre los dos grupos en el tiempo entre la administración de la solución y la necesidad de complementación analgésica. La dosis media del paracetamol utilizada en el primer día de la semana fue de 796 mg del G1 y de 950 mg en el G2; la complementación en la semana fue de 3578 mg G1 y 5333 mg en el G2.

CONCLUSIONES: El efecto analgésico de 1 mg de morfina y de 25 mg de bupivacaína a 0,25% sin vasoconstrictor intra-articular fueron semejantes.

INTRODUCTION

Primary osteoarthritis (OA) is a chronic disease of unknown origin and obscure pathogeny, with prevalence increasing with age. It affects synovial joints, especially load-bearing joints, being the knee the most frequently affected ¹. It may cause pain and movement limitation in a large percentage of elderly people.

Osteoarthritis-induced chronic pain has a major impact in the elderly, with different consequences: depression, decreased socialization, changes in sleep patterns, walking problems and increased demand for the health care system.

Osteoarthritis pain may be treated with anti-inflammatory drugs, opioids, acupuncture, laser, electric transcutaneous stimulation, capsaicin and ultrasound. Even with the association of these treatments, pain may persist and intra-articular administration of drugs is indicated. Several drugs are used for joint injection; most popular are steroids, with proven analgesic efficacy but undesirable side effects.

With the discovery of opioids peripheral receptors, these drugs have been intra-articularly used, although there are no controlled studies to prove their efficacy through this route in relieving osteoarthritis pain.

The purpose of this study was to compare the analgesic effects of intra-articular bupivacaine and morphine in knee osteoarthritis patients.

METHODS

After the approval of the Ethics and Research Committee, Universidade Federal de São Paulo, and with informed consent, 39 patients of both genders, aged 50 years or above, with clinical and radiological diagnosis of knee OA lasting for more than 3 months, at rest or in movement, and pain intensity above 3 in the numeric scale from zero to 10, were included in this study.

Exclusion criteria were patients in the acute phase of the disease, with blood, metabolic, inflammatory, infectious or tumoral disease, with previous knee or hip surgery as a consequence of the disease, with symptomatic and disabling hip OA and patients under opioids 24 hours before the study.

The study was randomized and double-blind, with patients divided in two groups: G1 (n = 18) was given intra-articular 1 mg (1 mL) morphine diluted in 9 mL of 0.9% saline and G2 (n = 21) received intra-articular 25 mg (10 mL) of 0.25% plain bupivacaine. Patients were placed in the sitting position with bended knee. After anti-sepsis, puncture was performed between the medial patella and the femoral condyle, with 25G needle through the skin, subcutaneous tissue and articular capsule, reaching the intra-articular space were the solution was slowly injected.

The following parameters were evaluated: pain intensity at rest and in movement by the numeric scale (before, 30 and 60 min and 7 days after drug administration) and by the verbal scale (for 7 days); analgesic duration at rest and in movement (30 and 60 min, and 7 days), need for first analgesic dose and total additional analgesic dose (500 mg paracetamol) in 7 days.

In addition, patients evaluated quality of analgesia (E = Excellent, G = Good, R = Regular, P = poor) 30 and 60 min, and 7 days after drug administration.

Results were analyzed by Mann-Whitney, Friedman, Kruskal-Wallis and Fisher Exact tests according to the nature of studied variables. Significance level was p < 0.05.

RESULTS

From 39 participants, 31 patients completed the study.

Groups were similar in age, height, weight, gender and body mass index (Mann-Whitney test, p < 0.05, Table I).

There was no statistically significant difference between groups in pain intensity at rest and in movement by the numeric and verbal scale in all studied moments (M0, M30, M60, M7), Mann-Whitney test (Table II and Table III).

Pain intensity significantly decreased after injection in both groups, both at rest and in movement (Friedman test, Table IV).

The time between intra-articular injection and need for additional analgesia was 594 ± 390 minutes after morphine (G1) and 733 ± 372 minutes after bupivacaine (G2), difference not statistically significant (Mann-Whitney test, p = 0.239).

Supplementation with paracetamol in the first day after intra-articular morphine (G1: n = 16) was 796 ± 1444 mg and 950 ± 1318 mg after bupivacaine (G2: n = 15), with no statistically significant difference between groups (Mann Whitney test, p = 0.452). Total paracetamol dose in one week for G1 (n = 16) was 3578 ± 2885 mg and for G2 (n = 15) it was 5333 ± 3782 mg, also with no statistically significant difference between groups (Mann-Whitney test, p = 0.2355).

Quality of analgesia 30 minutes after morphine infiltration in G1 (n = 18) was considered excellent by seven, good by nine, regular by one and poor by one of patients. After 60 minutes it was considered excellent by seven, good by seven and regular by four of patients. After seven days, analgesia was considered excellent by one, good by nine and regular by six of G1 patients (n = 16) (Figure 1).

In G2 (n = 21), 30 minutes after bupivacaine infiltration, quality of analgesia was considered excellent by six, good by 12, regular by three and poor by none of patients. After 60 minutes it was considered excellent by seven, good by 13 and regular by one of patients. After 7 days, analgesia was considered excellent by two, good by 11 and regular by two of G2 (n = 15) patients (Figure 2).

DISCUSSION

Our sample consisted mostly of female patients, in line with the literature, which shows a prevalence of OA among women above 45 years of age ^2,3. Age bracket above 55 years of age in our study is also close to data described in knee OA literature ^2,4.

Obesity is described as a major risk factor for OA, worsening pain ^5,6. In our study, patients had BMI &gt 29.7 ± 3.6 in both groups, characterizing an obese population.

Demographics data (gender, age, weight, height and body mass index) were similar between groups, thus making no difference in the pharmacologic action of the drugs. Although numeric and verbal scales are considered easy to understand and to apply, it has been observed that several patients had difficulties to associate lack of pain to zero and severe pain to 10, with no agreement of results between scales, both at rest and in movement.

Analgesic effect after injection was also evaluated by the first request for analgesic supplementation and total analgesics consumption during the study period, similarly to other studies ^7-10.

One week later, patients of both groups still remained with good analgesia; however, this effect was probably not solely promoted by intra-articular injection, because most patients made use of analgesic supplementation with paracetamol.

Both morphine (1 mg) and bupivacaine promoted pain relief at rest and in movement after 30 and 60 minutes. One week later, pain intensity was similar between groups; however, analgesic supplementation was needed and patients were given different paracetamol doses.

One week later, there was a decrease in the number of patients in both groups; some have not returned and others did not bring their pain diary. It is possible that some patients have not returned because they were still with no pain.

In a study with chronic OA pain patients, there has been significant pain relief 60 minutes after morphine injection, similarly to our study ¹¹. Authors have compared to placebo only after 60 minutes.

In acute postoperative pain, intra-articular morphine (1 mg) has not promoted pain relief as compared to placebo after 60 minutes, while bupivacaine (50 mg) did promote significant pain relief in this moment. However, 4 hours later these drugs have promoted significant analgesic effects as compared to placebo. After 24 hours, however, only morphine has maintained its analgesic action ⁷.

Acute pain is different from chronic pain, being more severe immediately after surgery and improving with time ¹².

Local anesthetics act by stabilizing the neuronal membrane through sodium channels blocking. Intra-articular bupivacaine inhibits nervous impulse conduction after 2 to 10 minutes, and its effect usually lasts longer as compared to other local anesthetics. Morphine promotes analgesia after binding to opioid receptors of the synovial tissue, decreasing excitability and action potential spread. Opioids also promote pro-inflammatory substances inhibition and have anti-inflammatory effects, in addition to decreasing the formation of bradykinin and plasma leakage. This explains long morphine onset in severe acute pain. When evaluated in chronic pain studies ^13,14, it shows significant pain relief at rest and in movement during the first hour after infiltration.

Analgesia duration, measured by the time for first analgesic request, was similar between groups. However, mean paracetamol dose was lower for G1 as compared to G2, both in the first day and during one week.

In our study, analgesia duration with morphine was 594 ± 390 and with bupivacaine it was 733 ± 372 minutes. In studies with chronic pain patients ^11,13-15, time elapsed for the first analgesic dose has not been described.

Analgesia duration with intra-articular bupivacaine after knee arthroscopy ¹⁶ was 442 min, and of intra-articular morphine it was 556 min ¹⁷, similar to our study. In other acute pain studies, analgesics were prescribed in fixed schedules ¹⁷ or just the 24-hour total consumption has been described ¹⁸.

Only one drug, paracetamol (500 mg), was standardized to be used at home as needed, thus preventing variations of analgesic potency with the use of different drugs. However, in spite of recommendations, some patients have used other analgesics and were excluded from the evaluation of mean consumption in 24 hours and 7 days.

There is a report in the literature on the use of three different analgesics for supplementation (acetyl-salicylic acid up to 300 mg, ibuprofen up to 800 mg and diclofenac up to 200 mg) during 6 days for chronic pain after intra-articular morphine or dexamethasone. The authors have not observed differences in consumption between groups; however, they have not informed the total dose of analgesics for each group ¹⁴.

In a study on acute postoperative pain, paracetamol consumption was lower in the intra-articular morphine group as compared to placebo in the first 24 hours ¹⁸. In other studies with acute pain patients, analgesic supplementation was also achieved with different analgesics ^7,8,17,19. There are few papers on intra-articular injection in chronic knee pain patients. A study has compared the analgesic effects and duration of intra-articular or intravenous morphine ¹³. A different one has obtained major pain relief at rest with 1 mg morphine associated to 10 mL of 0.25% bupivacaine in five patients who had poor response to previous treatment (oral anti-inflammatory or intra-articular steroid) ¹⁵. The effect of intra-articular morphine was also compared to intra-articular dexamethasone, but just during a single day ¹⁴. Intra-articular 0.25% bupivacaine was also compared with placebo after 24 hours and 7 days ¹¹, but no study has compared intra-articular morphine and bupivacaine for 7 days in chronic knee OA pain patients.

No study was found in the literature where treatment was evaluated by patients. This evaluation is important because not always total pain relief is considered an optimal result by patients. If there were side effects or complications, patients would rather have partial pain relief without other symptoms.

From our results, we may conclude that analgesic effects of intra-articular 1 mg morphine and of 25 mg of 0.25% plain bupivacaine are similar for that matter.

REFERENCES

Submitted for publication January 11, 2005

Accepted for publication May 9, 2005

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^*

Received from Disciplina de Anestesiologia, Dor e Terapia Intensiva da Universidade Federal de São Paulo, UNIFESP, São Paulo, SP

Publication Dates

• Publication in this collection
  13 Feb 2006
• Date of issue
  Oct 2005

History

• Accepted
  09 May 2005
• Received
  11 Jan 2005